p53 is required for 1,25-dihydroxyvitamin D-3-induced G(0) arrest but is not required for G(1) accumulation or apoptosis of LNCaP prostate cancer cells

1,25-Dihydroxyvitamin D-3 [1,25-(OH)(2)D-3] is an effective agent for inhibiting the growth of prostate cancer cells including LNCaP and PC-3 cell lines. However, the extent of growth inhibition in these cell lines differs because LNCaP cells are much more responsive than PC-3 cells. Previous studies in LNCaP cells have shown that 1,25-(OH)(2)D-3 treatment results in G(0)/G(1) cell cycle accumulation, loss of Ki67 expression, and induction of apoptosis. One difference between the two cell lines is that PC-3 cells lack functional p53, a protein that plays roles both in cell cycle regulation and induction of apoptosis. In this study, the role of p53 in 1,25-(OH)(2)D-3 action was examined using the p53-negative PC-3 cells and a line of LNCaP cells, called LN-56, in which p53 function was shut off using a dominant negative p53 fragment. We found that treatment with 1,25-(OH)(2)D-3 extensively inhibits growth of LN-56 prostate cancer cells lacking p53, but in contrast to the parental LNCaP cells, the LN-56 cells recover rapidly. Moreover, in prostate cancer cells, the synergism between 1,25-(OH)(2)D-3 and 9-cis retinoic acid appears to be dependent on the presence of functional p53; however, 1,25-(OH)(2)D-3-mediated induction of G, cell cycle accumulation and induction of apoptosis is not.